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Monoclonal Antibody Regulation of Protein Oligomerization

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Rat

Application Methods: Western Blotting

Background: The matrix metalloproteinases (MMPs) are a family of proteases that target many extracellular proteins including other proteases, growth factors, cell surface receptors, and adhesion molecules (1). Among the family members, MMP-2, MMP-3, MMP-7, and MMP-9 have been characterized as important factors for normal tissue remodeling during embryonic development, wound healing, tumor invasion, angiogenesis, carcinogenesis, and apoptosis (2-4). Research studies have shown that MMP activity correlates with cancer development (2). One mechanism of MMP regulation is transcriptional (5). Once synthesized, MMP exists as a latent proenzyme. Maximum MMP activity requires proteolytic cleavage to generate active MMPs by releasing the inhibitory propeptide domain from the full length protein (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The matrix metalloproteinase (MMP) family of proteases is a group of zinc-dependent enzymes that target extracellular proteins, including growth factors, cell surface receptors, adhesion molecules, matrix structural proteins, and other proteases (1, 2). Within this family, MMP1, MMP8, and MMP13 have been characterized as a collagenase sub-family of MMPs targeting fibrillar collagen (collagen type I, II, and III) for degradation. In addition to collagen, MMP1 also has activity toward a broad array of other ECM proteins such as fibronectin, gelatin, aggrecan (etc.), as well as growth factors, chemokines, and cytokines (3). MMP1 is widely involved in tissue remodeling during wound healing, tumor growth, invasion and metastasis, and arthritis (4-6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Bid is a pro-apoptotic “BH3 domain-only” member of the Bcl-2 family originally discovered to interact with both the anti-apoptotic family member Bcl-2 and the pro-apoptotic protein Bax (1). Bid is normally localized in the cytosolic fraction of cells as an inactive precursor and is cleaved at Asp60 by caspase-8 during Fas signaling, leading to translocation of the carboxyl terminal p15 fragment (tBid) to the mitochondrial outer membrane (2-4). Translocation of Bid is associated with release of cytochrome c from the mitochondria, leading to complex formation with Apaf-1 and caspase-9 and resulting in caspase-9 activation (5-7). Thus, Bid relays an apoptotic signal from the cell surface to the mitochondria triggering caspase activation (8,9).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: The Bcl-2 family consists of a number of evolutionarily conserved proteins containing Bcl-2 homology domains (BH) that regulate apoptosis through control of mitochondrial membrane permeability and release of cytochrome c (1-3). Four BH domains have been identified (BH1-4) that mediate protein interactions. The family can be separated into three groups based upon function and sequence homology: pro-survival members include Bcl-2, Bcl-xL, Mcl-1, A1 and Bcl-w; pro-apoptotic proteins include Bax, Bak and Bok; and "BH3 only" proteins Bad, Bik, Bid, Puma, Bim, Bmf, Noxa and Hrk. Interactions between death-promoting and death-suppressing Bcl-2 family members has led to a rheostat model in which the ratio of pro-apoptotic and anti-apoptotic proteins controls cell fate (4). Thus, pro-survival members exert their behavior by binding to and antagonizing death-promoting members. In general, the "BH3-only members" can bind to and antagonize the pro-survival proteins leading to increased apoptosis (5). While some redundancy of this system likely exists, tissue specificity, transcriptional and post-translational regulation of many of these family members can account for distinct physiological roles.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Bax is a key component for cellular induced apoptosis through mitochondrial stress (1). Upon apoptotic stimulation, Bax forms oligomers and translocates from the cytosol to the mitochondrial membrane (2). Through interactions with pore proteins on the mitochondrial membrane, Bax increases the membrane's permeability, which leads to the release of cytochrome c from mitochondria, activation of caspase-9 and initiation of the caspase activation pathway for apoptosis (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Absent in melanoma 2 (AIM2) is an interferon-inducible protein containing an amino-terminal pyrin domain and carboxy-terminal HIN-200 domain that functions in innate immunity and tumor progression (1). Expression of AIM2 can inhibit cell growth and tumor formation (2,3). Furthermore, the AIM2 gene has a high frequency of mutations associated with microsatellite-unstable colorectal cancers (4). AIM2 has a critical role in the activation of caspase-1, the protease responsible for the processing of pro-inflammatory cytokines IL-1β and IL-18. Caspase-1 activation is regulated by multi-protein complexes referred to as “inflammasomes” (5,6). Distinct inflammasome complexes have been described containing NLRP1/NALP1, NLRP3/NALP3, IPAF, and AIM2. The HIN-200 domain of AIM2 is responsible for binding to cytoplasmic double stranded DNA, resulting in caspase-1 activation. (7-9). This inflammasome complex also involves binding of the pyrin domain of AIM2 to the CARD-domain protein ASC/TMS1, which then interacts directly with caspase-1. As a result, AIM2 has been demonstrated to be an important sensor for a number of different pathogens (10-12).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, Noxa) is a small protein that plays a key role in mediating apoptotic signaling. Noxa is a pro-apoptotic Bcl-2 family protein that contains a single Bcl-2 homology (BH3) domain (1). Members of the “BH3-only” family (e.g. Noxa, Bad, Bim, Puma, Bid, Bik, and Hrk) are highly regulated proteins that induce apoptosis through BH3-dependent interaction with anti-apoptotic Bcl-2 family proteins (2). Noxa localizes to mitochondria and binds the anti-apoptotic proteins Mcl-1 and A1/Bfl-1, but does not bind to Bcl-2 or Bcl-xL (3). The Noxa protein competes with Mcl-1 for binding to mitochondrial Bak protein. Noxa was originally identified as a phorbol ester inducible protein that is highly expressed in adult T-cell leukemia cell lines (4). Several different stimuli, including DNA damage, hypoxia, interferon, viral infection, and double-stranded RNA, induce Noxa expression in cells. Higher levels of Noxa protein are typically found hematopoietic cells (3,5,6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunofluorescence (Frozen), Western Blotting

Background: SORL1, also called SorLA, is a 250 kDa type-1 membrane protein found in neurons of the central and peripheral nervous system (1). SORL1 is related to the yeast transporter Vps10p (2). While its exact function is unknown, because it shuttles between the Golgi apparatus and endolysosomal compartments, and given its structural similarity with Vps10p, it has been suggested that SORL1 acts in intracellular trafficking (3). Interestingly, SORL1 expression has been shown to be decreased in the brain of patients with Alzheimer's disease (4), and research studies have demonstrated a role for SORL1 as a neuronal sorting receptor that binds APP and regulates its trafficking and proteolytic processing, thus regulating the production of amyloid-beta peptides (5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).

$303
100 µl
APPLICATIONS
REACTIVITY
Rat

Application Methods: Western Blotting

Background: Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).

$260
100 µl
APPLICATIONS
REACTIVITY
Rat

Application Methods: Immunofluorescence (Frozen), Immunoprecipitation, Western Blotting

Background: The maintenance of glucose homeostasis is an essential physiological process that is regulated by hormones. An elevation in blood glucose levels during feeding stimulates insulin release from pancreatic β cells through a glucose sensing pathway (1). Insulin is synthesized as a precursor molecule, proinsulin, which is processed prior to secretion. A- and B-peptides are joined together by a disulfide bond to form insulin, while the central portion of the precursor molecule is cleaved and released as the C-peptide. Insulin stimulates glucose uptake from blood into skeletal muscle and adipose tissue. Insulin deficiency leads to type 1 diabetes mellitus (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Dynamin-related protein 1 (DRP1) is a member of the dynamin superfamily of GTPases. Members of this family have diverse cellular functions including vesicle scission, organelle fission, viral resistance, and intracellular trafficking (reviewed in 1). DRP1 affects mitochondrial morphology and is important in mitochondrial and peroxisomal fission in mammalian cells (2-5). The yeast ortholog of DRP1 clusters into a spiral-shaped structure on the mitochondrial membrane at the site of fission (reviewed in 6), and this structure is likely conserved in mammalian cells (3). The division of the mitochondria, which is required for apoptosis, as well as normal cell growth and development is controlled, in part, by the phosphorylation of DRP1 at Ser616 by Cdk1/cyclin B and at Ser637 by protein kinase A (PKA) (reviewed in 6). When phosphorylated at Ser616, DRP1 stimulates mitochondrial fission during mitosis. Conversely, fission is inhibited when DRP1 is phosphorylated at Ser637 (reviewed in 6). Dephosphorylation at Ser637 by calcineurin reverses this inhibition (7). In addition to phosphorylation, sumoylation of DRP1 is also an enhancer of mitochondrial fission (8). Balancing fission and fusion events is essential for proper mitochondrial function. Research studies have demonstrated mitochondrial defects in a variety of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease (reviewed in 6).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Phospho-p53 (Ser15) (16G8) Mouse mAb #9286.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Chromatin IP, Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$260
100 µg
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Chromatin IP, Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct immunofluorescent analysis in rat cells and flow cytometry in human and mouse cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Insulin (C27C9) Rabbit mAb #3014.
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Frozen)

Background: The maintenance of glucose homeostasis is an essential physiological process that is regulated by hormones. An elevation in blood glucose levels during feeding stimulates insulin release from pancreatic β cells through a glucose sensing pathway (1). Insulin is synthesized as a precursor molecule, proinsulin, which is processed prior to secretion. A- and B-peptides are joined together by a disulfide bond to form insulin, while the central portion of the precursor molecule is cleaved and released as the C-peptide. Insulin stimulates glucose uptake from blood into skeletal muscle and adipose tissue. Insulin deficiency leads to type 1 diabetes mellitus (2).